Ezetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1) protein, which mediates intracellular cholesterol trafficking from the brush border membrane to the endoplasmic reticulum, where chylomicron assembly takes place in enterocytes or in the intestinal absorptive epithelial cells. Cholesterol is a minor lipid constituent of chylomicrons; however, whether or not a shortage of cholesterol attenuates chylomicron assembly is unknown. The aim of this study was to examine the effect of ezetimibe, a potent NPC1L1 inhibitor, on trans-epithelial lipid transport, and chylomicron assembly and secretion in enterocytes. Caco-2 cells, an absorptive epithelial model, grown onto culture inserts were given lipid micelles from the apical side, and chylomicron-like triacylglycerol-rich lipoprotein secreted basolaterally were analyzed after a 24-h incubation period in the presence of ezetimibe up to 50 μM. The secretion of lipoprotein and apolipoprotein B48 were reduced by adding ezetimibe (30% and 34%, respectively). Although ezetimibe allowed the cells to take up cholesterol normally, the esterification was abolished. Meanwhile, oleic acid esterification was unaffected. Moreover, ezetimibe activated sterol regulatory element-binding protein 2 by approximately 1.5-fold. These results suggest that ezetimibe limited cellular cholesterol mobilization required for lipoprotein assembly. In such conditions, large lipid droplet formation in Caco-2 cells and the enterocytes of mice were induced, implying that unprocessed triacylglycerol was sheltered in these compartments. Although ezetimibe did not reduce the post-prandial lipid surge appreciably in triolein-infused mice, the results of the present study indicated that pharmacological actions of ezetimibe may participate in a novel regulatory mechanism for the efficient chylomicron assembly and secretion.

依泽替米贝抑制Niemann-Pick C1样1（NPC1L1）蛋白，该蛋白介导从刷状缘膜到内质网的细胞内胆固醇运输，在那里乳糜微粒组装发生在肠上皮细胞或肠吸收性上皮细胞中。胆固醇是乳糜微粒的次要脂质成分。然而，胆固醇的缺乏是否会减弱乳糜微粒的组装尚不清楚。这项研究的目的是检查有效的NPC1L1抑制剂依泽替米贝对上皮脂质转运以及肠上皮细胞的乳糜微粒组装和分泌的影响。将生长在培养插入物上的Caco-2细胞（一种吸收性上皮模型）从顶端切成脂质胶束，在存在依泽替米贝（50μM）的条件下孵育24小时后，分析了在基底外侧分泌的富含乳糜微粒的富含三酰甘油的脂蛋白。通过添加依泽替米贝（分别为30％和34％），脂蛋白和载脂蛋白B48的分泌减少。尽管依泽替米贝可以正常吸收胆固醇，但酯化作用却被取消了。同时，油酸酯化不受影响。此外，依泽替米贝将固醇调节元件结合蛋白2活化约1.5倍。这些结果表明，依泽替米贝限制了脂蛋白组装所需的细胞胆固醇动员。在这种情况下，在小鼠的Caco-2细胞和肠上皮细胞中诱导了大的脂质液滴形成，这表明未加工的三酰基甘油被掩盖在这些隔室中。